Progress during FY18: 1) A postdoctoral fellow, Mahamat Babagana, was hired in November 2017 to lead the plasma collection and cell-free DNA library generation efforts. We established a collaboration with the Matthias Meyer group in Max Planck Institute, Germany, where the original single-strand DNA library protocol was derived and is continuously being improved. Meyer and colleagues have provided valuable advice and technical information which we have implemented to generate 30 cfDNA libraries from plasma samples of AD patients, rheumatoid arthritis patients, and healthy controls. Both the Meyer lab and Mahamat have generated libraries which are being sequenced at the NCI CCR sequencing facility on their NextSeq sequencer to a sufficient depth, which will allow us to identify the samples that meet quality standards for deeper sequencing. The ultra-deep sequencing data will be analyzed for tissue-specific epigenetic signatures based on nucleosome occupancy and transcription factor binding. The bioinformatics postdoctoral fellow Jisu Ha is preparing to analyze the anticipated data with the computational footprinting methods by establishing an in-house analysis pipeline. 2) Sera to be used for Phip-Seq experiments have been identified and will be used in experiments as soon as the facility at Johns Hopkins School of Medicine can process our samples.